Crh Wildevuur

Distribution of exogenous surfactant in rabbits with severe respiratory failure : the effect of volume

ABSTRACT: The transient effect of surfactant therapy that is observed in some patients might, at least in part, be explained by a nonhomogeneous distribution. Therefore, we investigated the distribution of a surfactant preparation (Alvofact, 45 g/L) that is used clinically. Rabbits with severe respiratory failure were treated with this surfactant at a dose of 100 mg/kg body weight, and the distribution of surfactant was determined by the use of 141Ce-labeled microspheres that were mixed with the surfactant. Fifteen min after surfactant administration, the rabbits were killed, and the lungs were removed and divided into 200 pieces. The radioactivity per mg lung tissue was determined in each piece. We found that the endotracheal instillation of this surfactant preparation results in a nonhomogeneous distribution. However, a significantly improved distribution was obtained when this dose of surfactant (100 mg/kg body weight) was diluted with normal saline to a concentration of 6.25 g/L. The consequence of the administration of this dose was an intratracheal fluid administration of 16.0 mL/kg body weight. The distribution was also nonhomogeneous after the administration of a small-volume (2.4 mL/kg body weight), low-concentration surfactant preparation (6.25 g/L). We conclude that a surfactant preparation with clinical application is distributed nonhomogeneously in the lungs after endotracheal administration. The distribution can be significantly improved by increasing the fluid volume in which the surfactant is suspended.

Platelet preservation during cardiopulmonary bypass with aprotinin.

A remarkable reduction of postoperative blood loss after cardiopulmonary bypass (CPB) has been achieved by prophylactic treatment with the proteinase inhibitor aprotinin. To reveal the mode of action of aprotinin, 23 CPB patients were randomised for aprotinin (2 x 10(6) KIU in the pump prime) or placebo treatment during CPB. Blood samples were collected before and during operation. Blood loss and blood requirements were 50% lower in the aprotinin treated patients than in the untreated patients. The adhesive capacity of platelets assessed by the amount of platelet membrane glycoprotein Ib (GP Ib) decreased by 50% in the untreated patients within 5 min of CPB and remained low during CPB, whereas GP Ib did not decrease in the aprotinin treated patients. Fibrinogen degradation products indicating plasmin activity could only be measured after 30 min of CPB in the untreated, but not in the aprotinin treated patients. The kallikrein inhibiting capacity was 34% decreased in the untreated patients within 5 min of CPB, while it increased by 84% and remained high during CPB in the aprotinin treated patients. Our results demonstrate that the improved haemostasis during and after CPB in patients treated with aprotinin can be attributed to the preserved adhesive capacity of platelets. It remains to be found whether aprotinin has a primary effect on platelets or a secondary effect by plasmin or kallikrein inhibition.

The impact of heparin-coated cardiopulmonary bypass circuits on pulmonary function and the release of inflammatory mediators

Reduction of the inflammatory reaction with the use of heparin coating has been found during and after cardiopulmonary bypass (CPB). The question remains whether this reduced reaction also decreases the magnitude of CPB-induced pulmonary dysfunction. We therefore evaluated the effects of a heparin-coated circuit versus a similar uncoated circuit on pulmonary indices as well as on inflammatory markers of complement activation (C3b/c), elastase-&agr;1-antitrypsin complex, and secretory phospholipase A2 (sPLA2) during and after CPB. Fifty-one patients were randomly assigned into two groups undergoing coronary artery bypass grafting with either a heparin-coated (Group 1) or an uncoated (Group 2) circuit. During CPB, a continuous positive airway pressure of 5 cm H2O and a fraction of inspired oxygen (FIO2) of 0.21 were maintained. Differences in favor of the coated circuit were found in pulmonary shunt fraction (P < 0.05), pulmonary vascular resistance index (P < 0.05), and PaO2/FIO2 ratio (P < 0.05) after CPB and in the intensive care unit. During and after CPB, the coated group demonstrated lower levels of sPLA2. After CPB, C3b/c and the elastase-&agr;1-antitrypsin complex were significantly less in the coated group (P < 0.001). The coated circuit was associated with a reduced inflammatory response, decreased pulmonary vascular resistance index and pulmonary shunt fraction, and increased PaO2/FIO2 ratio, suggesting that the coated circuit may have beneficial effects on pulmonary function. The correlation with sPLA2, leukocyte activation, and postoperative leukocyte count suggests reduced activation of pulmonary capillary endothelial cells.

Improved recovery of cardiac function after 24 h of hypothermic arrest in the isolated rat heart: comparison of a prostacyclin analogue (ZK 36 374) and a calcium entry blocker (diltiazem)

Summary: The effects of a stable prostacyclin analogue (ZK 36 374; 4 nM) and a calcium entry blocker (diltiazem; 50 nM) on the recovery of cardiac function after 24 h of hypothermic (10°C) cardiac arrest were studied in the isolated rat heart. Recovery of the pressure – rate index of treated hearts was significantly better [59 ± 10% for diltiazem (p < 0.05) and 51 ± 7% for ZK 36 374 (p < 0.05)] than in untreated hearts (27 ± 9%). Untreated hearts had second- and higher-degree atrioventricular block, with an average ventricular rate of 60 ± 6% of control. All drugtreated hearts, however, were in sinus rhythm at their initial frequency without a significant alteration in PQ interval. Moreover, the incidence of severe arrhythmias was significantly reduced by ZK 36 374 (p < 0.02) and diltiazem (p < 0.01). ZK 36 374 reduced total purine overflow upon reperfusion (503 ± 51 vs. 223 ± 22 nmol min−1 g dry weight−1; p < 0.0005). The delayed overflow of adenosine, a proposed marker of reperfusion damage, was not affected by ZK 36 374 treatment. In contrast, diltiazem had no effect on total purine overflow upon reperfusion, but nearly abolished delayed adenosine overflow. It is concluded from these results that both ZK 36 374 and diltiazem improve myocardial recovery after 24 h of hypothermic cardiac arrest.

Comparison of three commercially available hollow fiber oxygenators : Gas transfer performance and biocompatibility

The new generation of oxygenators have improved blood flow pathways that enable reduction in priming volume and, thus, hemodilution during cardiopulmonary bypass (CPB). We evaluated three oxygenators and two sizes of venous reservoirs in relation to priming volume, gas transfer, and blood activation. To compare priming volume, gas transfer, and biocompatibility of three hollow fiber oxygenators and two different size venous reservoirs, 60 patients were randomly allocated in groups to undergo cardiopulmonary bypass. In each group, an oxygenator with a different surface area and priming volume was used: 1.8 m2 and 220 ml (group 1, n = 23), 2.2 m2 and 290 ml (group 2, n = 20), and 2.5 m2 and 270 ml (group 3, n = 17). In groups 1 and 3, a large soft shell (1900 ml) venous reservoir was used, whereas in group 2, a smaller soft shell (600 ml) venous reservoir was used. Gas transfer was assessed by calculating the oxygen transfer rate for each group and per square meter for each oxygenator group. Partial arterial oxygen pressure (paO2) and partial arterial carbon dioxide pressure (paCO2) between the groups were assessed with forward stepwise regression analysis. Biocompatibility was evaluated through measurement of platelet numbers, complement activation products (C3b/c), coagulation (thrombin anti-thrombin III complex), and fibrinolysis (plasmin anti-plasmin complex). No differences were found in oxygen transfer rate per group. However, when correcting the oxygen transfer rate for surface area, group 1 demonstrated a higher oxygen transfer rate compared with group 2 (p < 0.05) at an FiO2 of 40 and 60% and compared with group 3 at an FiO2 of 60 and 70%. The regression analysis showed that the average arterial pO2 was the highest in group 3, i.e., 79.2 mm Hg higher than in group 1 (p < 0.001) and 73.5 mm Hg higher than in group 2 (p < 0.001). Group 3 also had the lowest average arterial pCO2, 0.57 mm Hg lower than in group 1 (p = 0.004) and 0.81 mm Hg lower than in group 2 (p < 0.001). During CPB, platelet numbers decreased significantly in all groups (p < 0.001), without differences between the groups. C3b/c levels increased in all groups during CPB. At cessation of CPB the C3b/c level in group 2 (398 nmol/L−1) was significantly higher compared to group 1(251 nmol/L−1;p < 0.05) and group 3 (303 nmol/L−1;p < 0.05). Thrombin anti-thrombin III complexes and plasmin anti-plasmin complex complexes increased during CPB to significantly high levels at cessation of CPB, but there were no differences between the groups. The oxygenator with the smallest surface area and lowest priming volume (group 1) had the highest oxygen transfer rate per square meter and showed the least blood damage, as depicted by complement activation. The oxygenator with the largest blood contact surface area and improved geometric configuration (group 3) showed the lowest oxygen transfer rate per square meter. However, this oxygenator elevated oxygen partial pressure the most and reduced carbon dioxide partial pressure the most. In group 2, where a smaller venous reservoir was used, the highest blood activation was observed.

Autotransfusion of shed blood contributes additionally to blood saving in patients receiving aprotinin (2 million KIU)

Aprotinin decreases the hemoglobin content of shed blood significantly and thereby could potentially reduce the contribution of autotransfusion of shed blood to the blood-saving program. In part 1, by means of a prospective randomized study, we evaluated the effect of autotransfusion (AT) of shed blood on the reduction and avoidance of donor blood requirements in 40 matched patients undergoing internal mammary artery bypass (IMA) surgery and treatment with low-dose aprotinin (2 million KIU). Twenty patients (Group 1) received AT with a hard shell cardiotomy reservoir; twenty patients (Group 2, control) did not receive AT. In part 2, we studied at random the hemoglobin and total-protein content of shed blood in 10 patients of group 2 and in 10 IMA patients not receiving aprotinin. Retransfused patients required 0.1 +/- 0.3 units of donor blood versus 0.8 +/- 0.2 units in non-retransfused patients (not significant). The use of any blood product was avoided in 95% and 80% of the patients, respectively (not significant). Patients receiving aprotinin lost 50% less (P < 0.05) hemoglobin (62 g) and total-protein (28 g) in their drainage system than patients not receiving aprotinin. It was calculated that autotransfusion of about 530 ml of shed blood in aprotinin-treated patients, is equivalent to 0.4 units of homologous packed cells. In conclusion, autotransfusion of shed blood may contribute to blood saving in IMA patients treated with aprotinin, which reduces the shed blood hemoglobin and total protein content by 50%.

EFFECTS OF ACUTE BLEEDING ON OXYGEN-SUPPLY TO THE SKELETAL-MUSCLE IN DOGS

To study the effect of acute bleeding on the oxygen supply to the skeletal muscle, heparinized dogs were bled via an arterial cannula until mean arterial pressures of 25 and 50 mm Hg below initial value were reached. The shed blood was retransfused in reverse (50, 25 mm Hg) after correction of the acid-base imbalance in the dogs. Oxygen supply to the skeletal muscle was measured by means of a multiwire polarographic electrode placed on the sartorius muscle and was evaluated by means of ptO2 histograms. The ptO2 histograms showed that the oxygen supply to the skeletal muscle is severely impaired after a decrease in mean arterial pressure of 25 mm Hg. Further impairment was seen after a decrease in pressure of 50 mm Hg. During retransfusion tissue oxygenation was normalized only after all shed blood was retransfused and the initial mean arterial pressure was reached.

The priming of extracorporeal circuits: the effect on canine blood elements.

Improving hemocompatibility is of major interest in extracorporeal circulation (ECC). Changes in numbers and functions of the blood cells during ECC have been ascribed to the nonphysiologk materials of the circuit. In this study, commonly used priming fluids (banked blood, Ringers lactated solution, gelatin solution and dextran 70 solution) have been investigated for their influence on numbers and functions of canine thrombocytes, leukocytes and erythrocytes. Infusion of banked blood and Ringers lactated solution did not affect number and function of the thrombocytes, whereas the plasma expanders caused dramatic, but reversible decreases. Leukocyte numbers were also affected, but only gelatin resulted in a decrease of leukocyte function. No effect on erythrocyte numbers was observed. It is concluded that under these experimental circumstances some priming solutions cause acute intravascular aggregation. To obtain the optimal condition for studying the hemocompatibility of ECC, preferably Ringers lactated solution should be used.

Large volume instillation of surfactant during extracorporeal life support improves lung function in lung lavaged rabbits.

The sometimes limited effect of surfactant therapy in neonates might be explained in part by an non homogeneous distribution of the surfactant after endotracheal instillation. This distribution can be improved significantly by increasing the fluid volume. The aim of this study was to evaluate the effect of two methods for gas exchange during a large volume instillation of surfactant on the outcome of this treatment in lung lavaged rabbits. In the control group (n = 6) gas exchange was maintained with continuous positive pressure ventilation (CV), whereas in the other group gas exchange was established with extracorporeal life support (ECLS) (n = 6) and intermittent sighs. Five hours after surfactant administration, an identical weaning procedure was started in both groups. The authors found significantly higher PaO2 values in the ECLS group than in the control group in the normocarbia state. All animals in the ECLS group could be weaned to room air maintaining normal blood gases, whereas all the animals in the control group died in the course of weaning. The ventilator efficiency index was significantly higher during the weaning period in the ECLS group, indicating better lung function, than in the control group. The authors conclude that a large volume instillation of surfactant is feasible by applying ECLS and intermittent sighs. Additional studies are needed to elucidate if this combined treatment will be an improvement over current surfactant therapy.

CIRCULATORY EFFECTS OF SODIUM-NITROPRUSSIDE IN THE CONSCIOUS LAMB WITH AN AORTOPULMONARY LEFT TO RIGHT SHUNT

ABSTRACT: We studied the effect on the circulation of reducing peripheral vascular resistance by infusing sodium nitroprusside into lambs of three different age groups (subgroup A, 11-26 days, subgroup B, 32-52 days, and subgroup C, 61-88 days of age) with and without an aortopulmonary left to right shunt. Infusion of 10 μg/kg/ min nitroprusside over 2 h decreased aortic and left atrial pressures markedly and increased heart rate, whereas systemic, pulmonary, and left to right shunt blood flows hardly changed. Within 30 min after the onset of infusion, the hemodynamic variables stabilized. Aortic and left atrial pressures were still below control levels at that time. The different flows remained the same and heart rate, after an initial fall, increased again. The pattern of hemodynamic changes was not influenced by age or the presence of an aortopulmonary left to right shunt. Based on this study, we do not advocate sodium nitroprusside administration in case of a left to right shunt with normal arterial pressure and systemic blood flow.